Low-Dose Melphalan and Dexamethasone Compared With High-Dose Melphalan Followed By Autologous Stem Cell Transplant in Treating Patients With Primary Systemic Amyloidosis

NCT00477971 | Completed Phase 3 Results DMC

• 5 other identifiers: CDR0000546745P30CA015083MC04821691-05NCI-2009-01329
• Study Type: interventional
• Target: 89
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as melphalan and dexamethasone, work in different ways to stop the growth of plasma cells, either by killing the cells or by stopping them from dividing. Having an autologous stem cell transplant to replace the blood-forming cells destroyed by chemotherapy, allows higher doses of chemotherapy to be given so that more plasma cells are killed. By reducing the number of plasma cells, the disease may progress more slowly. It is not yet known whether combination chemotherapy is more effective than chemotherapy followed by an autologous stem cell transplant in treating primary systemic amyloidosis. PURPOSE: This randomized phase III trial is studying the side effects and how well giving low-dose melphalan together with dexamethasone works compared with high-dose melphalan followed by an autologous stem cell transplant in treating patients with primary systemic amyloidosis.

Conditions

Multiple Myeloma and Plasma Cell Neoplasm

Keywords

primary systemic amyloidosis

Outcome Measures

Primary Outcomes (1)

• Hematologic Response Rate

  Response that was confirmed on 2 consecutive evaluations during treatment. A hematologic response consisted of a Complete response, Very Good Partial Response or Partial Response. * Complete Response (CR): Complete disappearance of M-protein from serum and urine on immunofixation, normalization of Free Light Chain (FLC) ratio and \<5% plasma cells in bone marrow. * Very Good Partial Response (VGPR): \>=90% reduction in serum M-component; Urine M-Component \<=100 mg per 24 hours. * Partial Response (PR): \>=50% reduction in serum M-component and/or Urine M-Component \>=90% reduction or \<200 mg per 24 hours; or \>=50% decrease in difference between involved and uninvolved FLC levels.

  10 years

Secondary Outcomes (2)

• 3 Year Overall Survival

  3 years

• Organ Response to Treatment

  10 years

Study Arms (2)

Arm A

ACTIVE COMPARATOR

Patients receive low-dose melphalan IV over 15-30 minutes on day 1 or orally once daily on days 1-7 and oral dexamethasone on days 1-4 and 22-25. Treatment repeats every 6 weeks for 10 courses. Study treatment beyond one year is not allowed.

Drug: dexamethasone; Drug: melphalan

Arm B

EXPERIMENTAL

Patients receive filgrastim (G-CSF) on days -7 to -3 and undergo autologous hematopoietic stem cell (HSC) collection. Patients receive high-dose melphalan IV over 1 hour on days -2 and -1 and undergo autologous HSC transplantation on day 0.

Biological: filgrastim; Drug: melphalan; Procedure: autologous hematopoietic stem cell transplantation

Interventions

filgrastim BIOLOGICAL

No administration information given

Arm B

dexamethasone DRUG

Given orally

Arm A

melphalan DRUG

Given IV or orally

Arm A; Arm B

autologous hematopoietic stem cell transplantation PROCEDURE

Given on day 0

Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed primary systemic amyloidosis * Amyloid light-chain (AL) disease * Monoclonal protein by immunoelectrophoresis or immunofixation of the serum or urine OR abnormal free light-chain ratio * The following amyloid syndromes\* are allowed: * Amyloid hepatomegaly * Cardiomyopathy * Proteinuria * Peripheral or autonomic neuropathy * Soft tissue involvement including the tongue, submandibular tissues, and vascular claudication * Diffuse interstitial pulmonary AL disease allowed if pulmonary function is adequate to allow safe transplantation NOTE: \*Presence of amyloid deposits in a plasmacytoma or in bone marrow vessels in an asymptomatic patient does not constitute an amyloid syndrome * No secondary or familial amyloidosis * No multiple myeloma with lytic or destructive bone lesions or myeloma cast nephropathy * No multiple myeloma with \> 30% plasma cells in the bone marrow * No amyloidosis manifested only by carpal tunnel syndrome or purpura PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Platelet count ≥ 100,000/mm³ * Bilirubin ≤ 2.0 times upper limit of normal (ULN) * Alkaline phosphatase ≤ 6 times ULN * Creatinine ≤ 3.0 mg/dL * No NYHA class IV heart disease * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No uncontrolled infection * No HIV positivity PRIOR CONCURRENT THERAPY: * Prior alkylating agents, immunosuppressive drugs, or steroids allowed provided they were given for \< 1 month * Therapeutic steroid doses of ≤ 15 mg per day (or equivalent) allowed at discretion of physician * No concurrent participation in another clinical trial involving a pharmacologic agent

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell; Immunoglobulin Light-chain Amyloidosis

Interventions

Filgrastim; Dexamethasone; Melphalan

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Amyloidosis; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids

Results Point of Contact

• Title: Dr. Morie Gertz
• Organization: Mayo Clinic

gertz.morie@mayo.edu

Study Officials

• Morie A. Gertz, MD

  Mayo Clinic

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 23, 2007
• First Posted: May 24, 2007
• Study Start: October 1, 2005
• Primary Completion: July 1, 2012
• Study Completion: December 1, 2014
• Last Updated: May 17, 2016
• Results First Posted: July 21, 2015

Record last verified: 2015-06

Locations

US (1)